Echinococcus granulosus’ laminated layer immunomodulates nitric oxide, cytokines, and MMPs in PBMC from rheumatoid arthritis patients

Abstract

Abstract Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that affects the joints. Treatments are symptomatic and can induce side effects in some patients. In this sense and based on previous studies, our aim was to investigate the ex vivo immunoregulatory effect of the laminated layer (LL) during rheumatoid arthritis. LL is the outside layer of parasitic cyst of the helminth Echinococcus granulosus. Our main objective was to study the effect of LL on nitric oxide (NO) and cytokines production, matrix metalloproteinases (MMPs) activities, inducible NO synthase (iNOS) and nuclear factor κappa B (NF-κB) expression. In this context, cultures of peripheral blood mononuclear cells (PBMC) from Algerian RA patients in active (ARA) and inactive (IRA) stage of the disease were stimulated with LL extract (50, 100, 150μg/mL). However, PBMC from ARA patients were stimulated with methotrexate (MTX; 0.5μg/mL) and biological disease modifying anti-rheumatic drugs (bDMARDs): anti-TNFα (10μg/mL), anti-IL6 (10μg/mL), anti-CD20 (10μg/mL), alone or combined with LL (50μg/mL). Our results showed that LL reduced NO, TNF-α, and IL-17A production, MMP9/2 activities, and iNOS/NF-κB expression in PBMC from ARA patients. Concomitantly, LL increases IL-10 and TGF-β1 production in the same cultures. Interestingly, the decrease in NO production induced by bDMARDs was greater in association with LL. Collectively, our findings indicate a strong immunoregulatory effect of LL on NO, MMPs, and cytokines. LL probably acts through the NF-κB pathway. The development of biodrugs derived from LL of E. granulosus could be a potential candidate to modulate inflammation during RA.